2019 FDLI Annual Conference | Access materials at fdli.org/annual2019

Center for Devices and Radiological Health (CDRH)

Jeffrey E. Shuren, Director, Center for Devices and Radiological Health, FDAMahnu Davar, Partner, Arnold & Porter LLP

Heather S. Rosecrans, Executive Vice President, Medical Devices & Combination Products, Greenleaf Health, Inc.

Kristi Schrode Travers, Assistant General Counsel and Group Leader, Medical Device Regulatory Law, Johnson & Johnson

Moderated by Vernessa Pollard, Partner, McDermott Will & Emery LLP

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CDRH 2019 Update

Jeff ShurenMay 2, 2019

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Patients are at the Heart of What We Do

CDRH VisionPatients in the U.S. have access to high-quality, safe, and effective

medical devices of public health importance first in the world

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1,800Dedicated “CDRHers”

190,000Regulated Devices

18,000Device Manufacturing

Firms

21,000Device Manufacturing Facilities Worldwide

The Challenge

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The Misperception

Innovation and Safety

are not polar opposites but rather two sides of the same

coin

Innovation

Safety

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REALITY:CDRH has been advancing both safety and innovation for almost a decade

APPROACH: CDRH first enhances existing programs then advances innovative solutions and promotes global harmonization

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For the device industry to successfully innovate and for the FDA to optimally safeguard the public, the FDA must be

and must be supported to be innovative

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Outlines a vision for how CDRH can continue to enhance our programs and processes to assure:

• Safety of medical devices throughout the TPLC• Timely identification and resolution of safety issues• Advance innovative technologies that are safer, more effective and

address unmet needs

Establish Medical DeviceSafety Net

1 2

ExploreRegulatory Options

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SpurInnovation

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AdvanceCybersecurity

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Advance Use of

TPLC Approach to Device Safety

Ensure that FDA is consistently first among the world’s regulatory agencies to identify and act upon safety

signals related to medical devices

Medical Device Safety Action Plan

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FDA Device Inspections

• Firms are 8 times more likely to report a recall after 21 CFR 806 violations

• Firms report 3 times more adverse events following 21 CFR 803 violations

• FDA’s actions contributed to a 50% increase in annual number of voluntary recalls reported and a doubling in annual number of AERs since 2009

46%INCREASE

243%INCREASE

In the annual number of device inspections since

2007

In the annual number of foreign device inspections

since 2007

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MDSAP Participating Manufacturer Sites

Number of Sites AddedCumulative Total

U.S. (including territories)CanadaGermanyJapanChinaSwitzerlandUnited KingdomFranceItalyIreland

| 2014 | 2015 | 2016 | 2017 | 2018 | 2019

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• FDA announced its intention to harmonize and modernize the Quality System regulation for medical devices

• The revisions will supplant the existing requirements with the specifications of ISO 13485:2016

• The revisions will help harmonize domestic and international requirements

• This approach is consistent with and complements MDSAP

See Spring 2018 Unified Agenda of Regulatory and Deregulatory Actions

FDA Quality System Regulation and 13485

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Novel Approaches to Promoting Product Quality

Case for Quality2011

MDIC Collaborative

Forum2014

Voluntary Quality Maturity Appraisal Pilot2018

• Third-party certified by Capability Maturity Model Integration Institute (CMMI) conducts appraisal

• Collaboration and feedback on quality objectives• Removal from the surveillance work plan• Reduction in manufacturing submission requirements

and faster approval for implementation• Waive some pre-approval inspections

23 participating firms >35 appraisals 86% report appraisal had a

positive impact on product quality

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Device Safety 2019

• MDIC to develop a governance structure for Case for Quality Voluntary Improvement Program

• MDIC/NEST Coordinating Center task force to develop active surveillance roadmap

• CDRH to issue draft guidance on the Safer Technologies Program (STeP)• CDRH to issue peer-reviewed white paper on hypersensitivity to metal

implants and hold advisory panel

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25 29

61 61 5171 86 91

98 106

0

20

40

60

80

100

120

2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Novel Device Approvals

* Novel devices include original PMAs, panel track supplement PMAs, de novos, HDEs and breakthrough 510(k)s

>4-fold Increase in # of Novel Device Approvals

Calendar Year

15

442

215

101

30 30 30 30

0

100

200

300

400

500

2011 2013 2014 2015 2016 2017 2018

Clinical Trials (IDEs)*

>90% Reduction in Time to IDE Approval

Median number of days to full IDE approval

Fiscal Year

* IDE=Investigational Device Exemption

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Early Feasibility Studies: Perceptual Shifts in Ease of Conduct

2014 2015 2016 20181 Australia Australia Australia Australia

2 New Zealand New Zealand New Zealand United States

3 Central America Canada Canada Central America

4 Germany Netherlands Netherlands New Zealand

5 Denmark Germany Denmark Canada

6 Netherlands United States United States Germany

7 Canada Central America Central America Brazil

8 Brazil Denmark Germany Netherlands

9 United Kingdom United Kingdom Brazil France

10 United States Brazil United Kingdom United Kingdom

*Data provided by Aaron Kaplan/Dartmouth Device Development (3D) Symposium Annual Survey of 3D Participants

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Importance of Early Feasibility Studies

• Earliest patient access• Close collaboration between

developers & users• Clinical study continuity from

early clinical use to post-approval

• U.S. leadership and contributor to medical device innovation

U.S. Sites Re-engaging in Early Clinical Research

MDIC to begin EFS Clinical Site Consortium Pilot

FDA Early Feasibility Study Program 2015-2018

>50 >180 121% Company

ParticipantsEarly

Feasibility IDEs

Approved

Increase in Annual # of EFS IDEs Approved

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National Evaluation System for health Technology

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FDA Has Taken Steps to Strengthen the 510(k) Program

2014 Foundational Guidance• Established concept of primary predicate and reference devices• Clarifies when a change in indication is a new intended use• Addresses when technological differences raise different questions of

safety and effectiveness

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Modernized Approach to 510(k) Device ModificationsFinal Guidance 2017

• Clarifies when device modifications require a new 510(k)

• Relies on Quality System regulation

• Leverages risk-based assessments and risk management principles

• Clarifies role of testing (i.e. verification and validation activities)

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Eliminated the Use of Some 510(k) Devices as Legal Predicates

1477 Number of 510(k) cleared devices eliminated for use as legal predicates since 2012

84% of devices eliminated for use as 510(k) predicates have been eliminated since 2012

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More Information – More Thorough Review

1185 Average number of pages in a 510(k) in 2017

150% Increase in the number of pages per 510(k) since 2009

32% increase in the time spent by FDA review staff reviewing each 510(k) submission since 2009

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Moderate Risk Devices - 510(k)

93.596.4

97.3

98.8 98.7

98.7

97.6

99.7 99.5

90

92

94

96

98

100

2010 2011 2012 2013 2014 2015 2016 2017 2018

92% REDUCTION in Files that Miss Day 90

Fiscal Year

Decision within 90 FDA Days*

*Comparison of Receipt Cohorts 15 months After Start of FY

Perc

ent

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Introduced “SMART Template”

• Formatted guide/template for review staff

• Promotes consistency in review and documentation

• Includes links to help/advice to facilitate review

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Quality 510(k) Review Pilot Program

• “Turbotax” for 510(k)• Sponsor completes formatted eSubmission• In return, CDRH will:

• Skip RTA phase• Commit to interactive review without hold (where

possible)• Strive to reduce FDA review time by 1/3 (goal: 60 days)

Launched Pilot (for ~ 40 product codes) Fall 2018

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Imagine: Single Submission

• Regulatory Submission with Common Data Elements

• Electronic Submission• IMDRF Work Item to define

common ‘Table of Contents’

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Safety and Performance Based Pathway

• Moderate risk devices are evaluated through 510(k) Program

• Require demonstration of “substantial equivalence” to a predicate device

• Direct comparison to a predicate device may be burdensome and unnecessary

• Abbreviated 510(k) submission program relies on guidance documents, special controls, and FDA-recognized consensus standards to facilitate 510(k) review

Guidance Issued on February 1, 2019 Expands Abbreviated 510(k)

Approach

• Optional approach for certain, well-understood device types

• Demonstrate new device meets FDA-identified performance criteria based on performance of modern predicates

• Transparency about device performance for health care providers and patients

• Provides opportunities for international harmonization and support the establishment of a Medical Device Single Review Program

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Modern Predicates

• Nearly 20% of 510(k)s are cleared based on predicates that are > 10 years old

• That does not make them inherently unsafe

• The goal in focusing on older predicates is to drive sponsors to offer patients devices with the latest improvements and advances

CDRH is considering making public on its website those cleared devices

that demonstrated substantial equivalence to older predicate

devices

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142 devices accepted into the program since April 2015

1st breakthrough device approved December 2017

11 breakthrough devices granted marketing authorization

Breakthrough Devices Pathway (Formerly Expedited Access Pathway)

• Interactive & Timely Communication

• Pre-Postmarket Balance

• Flexible Clinical Study Design

• Senior Management Engagement

• Priority Review

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Consideration of Uncertainty In Making Benefit-Risk Determinations in PMA, De Novo, and HDE Approvals

• Some degree of uncertainty generally exists around benefits and risks for regulatory decisions

• The regulatory standard is reasonable assurance – not absolute assurance

• Flexible regulatory paradigm

Clarified Through Draft Guidance Issued on September 5, 2018 the Circumstances Where FDA is More Likely to Accept More Uncertainty

• For example: – Breakthrough Devices– PMAs with small patient population– De Novos with minimal risk– Particularly if established postmarket data collection

mechanism

• Provides opportunities for international harmonization, where appropriate, and supports the establishment of a Medical Device Single Review Program

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Digital Health Program

TECH POLICY SUPPORT

Manage/Respond to Inquiries

• Regulatory Submissions Support

• Policy Implementation

• Identify and develop staff training

POLICY DEVELOPMENT

Cybersecurity Interoperability

• Artificial Intelligence / Machine Learning

• Software Policies under 21st

Century Cures Act

• Policy Intelligence

CENTER OF

EXCELLENCE

Unified and collaborative environment; applying best practices, conducting research, support, training for

software and digital health technologies.Supplementing bench strength @ FDA

STRATEGIC INITIATIVES

Explore tailored pathway: Software Precertification Pilot

• Medical Device Interoperability

• Cybersecurity

STRATEGIC PARTNERSHIP

harmonization through IMDRF

• Strategic Industry partnership

• Academic partnership

• Federal partnerships:

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The IMDRF Good Regulatory Review Practices (GRRP) working group has focused efforts on harmonizing premarket requirements in alignment with the IMDRF strategic priority to improve the effectiveness and efficiency of premarket review.

Imagine: Single Review

IMDRF GRRP WG/ N40

FINAL:2017Competence, Training, and

Conduct Requirements

IMDRF GRRP WG/ N47

FINAL: 2018Essential

Principles of Safety and

Performance

IMDRF GRRP WG/N52

FINAL: 2019 Principles of

Labelling

NWIP: Recognition

Requirements for Premarket

Review Organizations

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IMDRF GRRPCurrent Work Item

• Developing a conformity assessment/recognition program for medical device premarket review organizations – Models the Medical Device Single Audit Program (MDSAP) by leveraging existing documents

where possible and making modifications as necessary to accommodate premarket review requirements

– Utilize some requirements outlined in ISO/IEC standards (e.g. ISO/IEC 17065) • Draft document to be submitted to IMDRF MC in June 2019 for public consultation

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CDRH Reorganization

Establish the Office of Product Evaluation and Quality (OPEQ) -Combines the Offices of Compliance, Office of Device Evaluation, Office of Surveillance and Biometrics and the Office of In Vitro Diagnostics and Radiological Health into one “super office” focused on a Total Product Lifecycle approach to medical device oversight.

Establish the Office of Policy (OP) - Establishes two teams, the Guidance, Legislation and Special Projects Team and the Regulatory Documents and Special Projects Team. There are no changes in the functions for CDRH Policy.

Establish the Office of Strategic Partnerships and Technology Innovation (OST) - Combines the Science & Strategic Partnerships, Digital Health, Health Informatics and Innovation teams. There are no changes in functions within the different teams.

OPEQ

Once fully implemented, the CDRH reorganization will:

OP

OST

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CDRH (Before Reorganization)

Office of the Center Director

(OCD)

Office of Communication and Education

(OCE)

Office of Management

(OM)

Office of Science, and Engineering Laboratories

(OSEL)

Office of Surveillance

and Biometrics (OSB)

Office of In Vitro

Diagnostics and

Radiological Health (OIR)

Office of Device

Evaluation (ODE)

Office of Compliance

(OC)

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CDRH (After Reorganization)

Office of Strategic

Partnerships and Technology Innovation

(OSPTI)

Office of Management

(OM)

Office of Science and Engineering

Laboratories (OSEL)

Office of Communication and Education

(OCE)

Office of Policy(OP)

Office of Product Evaluation and

Quality(OPEQ)

Office of the Center Director

(OCD)

(OST)

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For the device industry to successfully innovate and for the FDA to optimally safeguard the public, the FDA must be

and must be supported to be innovative

Do you believe the FDA has the right tools, authorities, and support to be

optimally innovative?

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Thank You

2019 FDLI Annual Conference | Access materials at fdli.org/annual2019

Center for Devices and Radiological Health (CDRH)

Jeffrey E. Shuren, Director, Center for Devices and Radiological Health, FDAMahnu Davar, Partner, Arnold & Porter LLP

Heather S. Rosecrans, Executive Vice President, Medical Devices & Combination Products, Greenleaf Health, Inc.

Kristi Schrode Travers, Assistant General Counsel and Group Leader, Medical Device Regulatory Law, Johnson & Johnson

Moderated by Vernessa Pollard, Partner, McDermott Will & Emery LLP